A Companion Sample Collection Protocol to Support the Discovery of Breast Cancer Aberrations With Treatment of CDK4/6 Therapy/LEE011/Ribociclib

• ClinicalTrials.gov Identifier: NCT03050398
• Recruitment Status: Terminated
• First Posted: February 10, 2017
• Results First Posted: May 15, 2020
• Last Update Posted: May 28, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This study was a companion study to CLEE011A2404 which provided the opportunity for the collection of tumor tissue samples to better understand relevant mutations and the mechanisms responsible for resistance to treatment.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Ribociclib; Drug: letrozole	Phase 3

Detailed Description:

This was a multicenter, non-treatment based companion sample collection protocol conducted in the US only. This protocol sought to evaluate the aberrations of common pathways for newly diagnosed HR+/HER2- advanced breast cancer tumors and responses to ribociclib in diverse patient populations. This companion sample collection protocol was available for all US patients enrolled on CLEE011A2404 (CompLEEment-1) and did not alter the planned treatment. Tumor collection required for this study occurred at two time points: at baseline/screening and upon the development of progressive disease as shown in the protocol. Patients eligible for this companion study were required to sign an optional additional consent form at the time of enrolling into the core trial.

After eight patients had consented and samples had been taken, it was determined that the companion study protocol had not been properly initiated or monitored at the sites. This was determined to be a significant GCP violation and the clinical team made the decision to terminate the trial. In addition to the GCP issues, enrollment had been closed to the core study so enrolling additional patients was no longer possible. The limited number of samples would not provide any meaningful analysis. The samples were never analyzed. The study was not terminated due to safety or efficacy concerns. Samples collected were either destroyed or will be retained for up to 15 years based upon the decision of the patient.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Companion Sample Collection Protocol to Support the Discovery of Breast Cancer Aberrations With Treatment of CDK4/6 Therapy/LEE011/Ribociclib
• Actual Study Start Date: June 7, 2017
• Actual Primary Completion Date: March 8, 2019
• Actual Study Completion Date: March 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: ribociclib + letrozole; ribociclib with letrozole per the core study	Drug: Ribociclib; ribociclib + letrozole; Drug: letrozole; ribociclib + letrozole

Outcome Measures

Primary Outcome Measures :

1. Identify Mutations of Genes From Tissue Samples Between Baseline and Time to Progression to Determine Modes of Resistance to Ribociclib After Disease Progression [ Time Frame: Baseline, time of progression approximately 24 months ]
   Mutations of genes that were relevant to HR+ and the CDK4/6 pathway such as but not limited to CCND1, CDKN2A, PIK3CA and PTEN to identify the potential mechanisms of progression.

Secondary Outcome Measures :

1. Compare the Differences in Mutations Across Various Races / Ethnicities Based on Baseline Samples [ Time Frame: Baseline, time of progression approximately 24 months ]
   Change in mutations would have been assessed based on baseline samples and compared across diverse races/ethnicities with HR+ HER2- advanced breast cancer - specifically Caucasian, African America, Hispanic, Native American and Pacific Islander.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent was to have been obtained prior to any baseline/screening procedures.
• Patients eligible for this companion sample collection protocol sample collection protocol must have met all inclusion in CLEE011A2404.

Exclusion Criteria:

• Patients eligible for this companion sample collection protocol must not have met any of the exclusion criteria in the CLEE011A2404 study, in addition to the following:
• Patients without either fresh or archival tumor tissue accessible.

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology Associates PC HAL

Sedona, Arizona, United States, 86336

United States, California

Pacific Shores Medical Group SC

Long Beach, California, United States, 90813

United States, North Carolina

Oncology Speciialists of Charlotte

Charlotte, North Carolina, United States, 28207

United States, South Carolina

McLeod Center for Cancer Treatment and Research

Florence, South Carolina, United States, 29506

Carolina Blood and Cancer Care of South Carolina

Rock Hill, South Carolina, United States, 29732

United States, Washington

PeaceHealth St Joseph Medical Center

Bellingham, Washington, United States, 98225

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol and Statistical Analysis Plan  [PDF] December 15, 2016

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03050398
• Other Study ID Numbers: CLEE011AUS42
• First Posted: February 10, 2017
• Results First Posted: May 15, 2020
• Last Update Posted: May 28, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

HR-positive; HER2-negative; Advanced breast cancer; LEE011; ribociclib; letrozole; femara; CDK; CDK4; CDK6; CDK4/6; CDK4/6 inhibitor; Phase III; Phase IIIb; ER-positive; PR-positive; Postmenopausal; Premenopausal; Men

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Letrozole; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs